The present invention applies to medicine, more specifically, to pharmacology and it can find applications in pharmacotherapy for all kinds of diseases including decrease of organism intoxication under taking medicines.
A search for ways of strengthening of medicines action on the human organism goes on for a long time. It is connected both to insufficient therapeutic effect of the compound and to its insufficient quantity which is applied for treatment and cannot be increased owing to onset of its toxic effect as far as practically all the compounds exert an adverse effect including non-allergic negative side effect, allergic reactions, toxic effects, etc. [1]. Manifestations of non-allergic side effect include only the effects which appear under application of compounds in therapeutic doses and compose a spectrum of their pharmacological action. Thus, under application of tranquilizers quickness of mental and-physical reactions decreases, sleepiness appears; in the case of analgetics, e. g., acetylsalicylic acid, ulcerogenic action and other side effects are observed.
Side effects can be primary and secondary ones. The primary effect appears as a direct result of the present medicine influence on a certain substrate (e. g., nausea, vomiting under an irritating action of a compound on a mucous membrane of the stomach). The secondary side effect concerns unfavorable side influences (e. g. hypovitaminosis as a result of intestinal flora suppression with antibiotics) [1]. Unfavorable effects of compounds are highly diverse by their character; they have unequal expression and different duration. Side effects can be directed towards the nervous system, blood and hematogenesis, blood circulation organs, respiration, digestion, kidneys, endocrine glands, etc. Some side effects are endured relatively easily (moderate nausea, headache, etc.), other ones can be serious and even dangerous for life (liver affection, leucopenia, aplastic anemia) [1]. Negative influences exerted by medicaments also include allergic reactions, frequency of which is high enough. They appear independently from the dose of applied compound [1]. Clinical picture of allergic reactions is very different. There can appear urticaria and other skin erruptions, angioneurotic edema, serum sickness, bronchial asthma, breach of hemopoiesis, fever, hepatitis, cholestatic jaundice, anaphylactic shock, etc. [1].
Idiosyncrasy is another possible cause of unfavorable responses to compounds. Compounds cause toxic effects in doses over therapeutic ones. The last named generally manifest themselves as some serious breaches of functions of organs and systems (hearing decrease, vestibular disturbances, blindness as a result of optic nerve lesion, an expressed breach of stimulation conduction via the myocardium, liver lesion, breach of hemopoiesis, suppression of vitally important centers of medulla oblongata). The main cause of toxic effects is overdosagexe2x80x94occasional or deliberate exceeding of maximum permissible doses. Moreover, accumulation of toxic concentrations of compounds in the organism is possible as a result of breaches of their metabolism (e.g., under liver pathology) or under slow excretion of these (under some kidney diseases). Being prescribed during pregnancy medicaments can exert a detrimental effect on the embryo and fetus. Such effects include teratogenic impact of compounds, which causes birth of children with various anomalies [1]. Medicaments can possess mutagenous and embryotoxic properties. These properties are especially intrinsic for antitumoral agents. In the case of some compounds drug dependence can develop under repeated application. It manifests itself as irresistible yearning for application of the compounds, usually with the aim of improvement of mood or with the purpose to feel better, to get rid of suffering or unpleasant senses and feelings including ones which appear under abolition of compounds causing the drug dependence.
Psychical drug dependence and physical one are recognized. In the case of psychical drug dependence discontinuance of the drugs application (e. g., cocaine or hallucinogens) leads only to emotional discomfort. Under application of some compounds physical drug dependence can be in progress. In this case abolition of the drug causes grave condition which, in addition to acute psychical changes, manifests itself as various and often serious somatic breaches connected to functional disorder of many systems of the organism. This is the so called abstinence syndrome or deprivation phenomenon [1]. A search of ways for reduction of unfavorable effects of medicaments goes on for a long time. A big number of compounds for the specific treatment of drug poisoning, which are called antidotes and antagonists, include compounds which inactivate poisons either via chemical and physical interaction or at the sacrifice of pharmacological antagonism (at the level of physiologic systems, receptors, etc.). Thus, under intoxication with heavy metals, compounds are applied which form non-toxic complexes with the metals (e.g., unithiol, penicillamine, CaNa2EDTA). Antidotes are known, which react with the compound and release the substrate (e. g., oximes, which are cholinesterase reactivators; antidotes, which are applied under intoxication with methemoglobin formers, act in a similar way). Pharmacological antagonists are of considerable use under acute poisonings (atropinexe2x80x94under poisoning with anticholinesterase agents, naloxonexe2x80x94under poisoning with morphine, etc.). Pharmacological antagonists usually enter into competitory interactions with the same receptors, which interact with the compounds which caused the poisoning [1]. However, antidotes and antagonists are specific compounds characteristic for a specyfic type of intoxications and these are not applied under application of medicaments in therapeutic doses [1]. Antidotes and antagonists are not applied as complexes with medicaments.
To expand medicaments effect spectrum and promote pharmacological effect of compounds and decrease their toxicity, compounds with various composition were investigated including organogermanium ones.
Among organogermanium compounds (OGC), therapeutic effect of 2-carboxyethyl-germanium sesquioxide (O1,5GeCH2 CH2COOH)n and its derivatives has been much investigated. Authors applied this compound and its derivatives as original medicaments. There exist examples of its applications in cosmetics, as a nutrition additive and as an original medicament [2]. 2-Carboxyethylgermanium sesquioxide and its derivatives have been much investigated as original anticancerogenic medicaments in clinics and found not sufficiently powerful [2].
The medicament manifested therapeutic effect in high doses, usually 100-200 mg/day, what, as it has been found later, leads to various health breaches [2]. The authors have not claimed a universal effect for expansion of the medicaments effect spectrum, strengthening of pharmacological effect of the compounds and decrease of the drug toxicity [2-11].
To promote the main pharmacological effect, medicaments are often applied on the background of various stimulants (e. g., specific antibacterial therapy on the background of immunostimulation).
Applied in therapeutic practice, immunopotentiators are the closest by their effect to the claimed compounds.
Medicaments, which stimulate (normalize) immune reactions, are applied in complex therapy of immunodeficient states, chronic infections and malignant tumors. Biogenic substances are applied as immunopotentiators (thymus preparations, interferon, BCG vaccine) and synthetic compounds (Levamisolum, sodium diethylthiocarbamate, etc.) [1].
Tactivinum (T-activin) normalize quantity and function of T-lymphocytes (in immunodeficient states), stimulates production of lymphokines, xcex1- and xcex2-interferons, rehabilitates suppressed production of T-killers and in general increases cell immunity tension. It is applied in immunodeficient states (after radiotherapy and chemotherapy for oncologic patients, under chronic purulent and inflammatory processes, etc.), under lymphogranulomatosis and also under disseminated sclerosis [1].
Interferon is known mainly thanks to its antiviral activity. At the same time it has been shown that it causes favorable influence on the course of immune processes. In combination with another medicaments it is applied in therapy of some infections (e. g., hepatitis) and also neoplasms (especially under myeloma and lymphoma from B-cells) [1].
The BCG vaccine is applied for vaccination against tuberculosis. At the present time the BCG vaccine is applied in complex therapy for a number of malignant tumors.
The BCG vaccine stimulates macrophages and, obviously, T-lymphocytes. Favorable effect has been recorded under acute myeloid leukemia, some kinds of lymphoma (unrelated to Hodgkin""s lymphoma), under cancer of intestine and mammary glands [1].
Levamisolum (Decaris) belongs to synthetic preparations. It is applied in the form of hydrochloride. There are indications that Levamisolum causes stimulating influence on macrophages and T-lymphocytes. It does not modify production of antibodies. Consequently, the main effect of Levamisolum manifests itself in normalization of the cellular immunity. It is applied under immunodeficient states, some chronic infections and a number of tumors.
Levamisolum is prescribed in combination with specifically effecting preparations. It is applied inwardly. After its single taking side effects practically are not observed. At the same time after repeated takings of Levamisolum, especially if its doses are high, many side effects are observed, including more serious ones. Thus, allergic reactions can manifest themselves (eruption, fever, stomatitis), suppression of hemopoiesis (neutropenia, agranulocytosis). Besides, neurological breaches are observed (excitement, insomnia, headache, vertigo) and dyspeptic effects (nausea, vomiting, diarrhea) [1].
However, none of the immunopotentiators being used does exhibit any universal expansion of the medicaments effect spectrum, strengthening of pharmacological effect of the compounds and decrease of the drug toxicity.
All the immunopotentiators listed here possess side effects and are unsuitable for long and constant use. [1]. The method by the source [1]is taken as the prototype for the claimed method.
The present invention allows to overcome the above mentioned shortcomings of Levamisolum application and to ensure expansion of the medicaments effect spectrum, strengthening of pharmacological effect of the compounds and decrease of the drug toxicity for medicaments both of organic origin and of inorganic one independently of the kind of medicament and the kind of disease.
According to the invention, there is provided a substance for human and animal use, e.g., for therapeutic, prophylatic, alimentary or hygienic purposes comprising a complex of at least one medicament or biologically active compound with at least one chemical compound, characterized in that the chemical compound comprises an organogermanium compound (OGC) and the complex has the general formula (I):
Lk(OGC)m(Solv.)nxe2x80x83xe2x80x83(I)
Where
kxe2x89xa71
mxe2x89xa71
nxe2x89xa70
L: a medicament or a biologically active compound
Solv.: an inorganic or organic solvent
It has been found that complexes of medicaments with organogermanium compounds remarkably expand drug action spectrum, promote pharmacological effect and decrease drug toxicity of both the medicament and the organogermanium compound.
Preferably, said organogermanium compound corresponds to 1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane having a general formula (II): 
where:
Rxe2x80x94an organic radical or hydroxyl or thiohydroxyl or elementoorganic radical
R1÷R12xe2x80x94hydrogen or an organic radical, oxygen (under substitution of R1R2; R5R6; R9R10);
X=oxygen or sulfur.
According to another embodiment of the invention, the organogermanium compound corresponds to:
1-germa-2,8-dioxa-5-azabicyclo[3.3.01,5]-octane having the general formula (III): 
where
Rxe2x80x2Rxe2x80x3; an organic or elementoorganic radical,
R1-R9: hydrogen or an organic radical, oxygen (by substitution of R1R2, R5R6)
The main types of medicaments and biologically active substances do compound with organogermanium groups. Taking the example of 1-germa-2,8,9-trioxa-5-azatricyclo [3.3.3.01,5]undecane, the chemical interaction can be explained according to the following three main types of interactions:
1. Formation of hydrogen bonds between the hydroxyl (thiohydroxyl) group of an OGC and hydroxy-, carboxy-, oxo-, amino-, sulpho-, mercapto- and other groups, and also their thioanalogs, anions of organic and inorganic salts and other groups of medicaments and biologically active compounds. 
2. Expansion of coordination sphere of the germanium atom up to 6 as a result of donor-acceptor interaction of functional groups of medicaments and biologically active compounds mentioned in Item 1 with the atom of germanium. 
3. Donor-acceptor interaction of the nitrogen atom in the molecule of an OGC with carboxy(thiocarboxy)group of a medicament or a biologically active compound. 
where Rxe2x80x2: an organic radical.
Mixed types of such complexes can also be observed. Application of complex compounds of medicaments (L) with OGC having the general formula (I, II or III) leads to substantial expansion of the medicaments effect spectrum, strengthening of pharmacological effect of the compounds and decrease of toxicity of medicaments and biologically active compounds.
Complex medicaments, in addition to their pharmacological effect, acquire the following pharmacological properties: antitoxic, antiinflammatory, antihypoxic, immunopotentiating, repairing, nootropic ones. If the medicament already possesses the listed pharmacological properties, so the listed pharmacological properties will be considerably strengthened. The main pharmacological property of the medicament will also be strengthened.
Hypoxy, stimulation of lipids peroxide oxidation, immunodepression, development of inflammatory processes are universal mechanisms for development of practically any pathology. Thus, a complex medicament blockades various stages of disease development, increases resistance of the organism resulting in strengthening of the main therapeutic effect and also in decrease of the complex medicament toxicity. Expansion of medicament effect spectrum, strengthening of therapeutic effect and decrease of toxicity are observed on formation of complexes with any one of medicaments and biologically active compounds: aminoacids, vitamins, nucleic acids and their components, carbohydrates, lipids, fatty acids, ferments, hormones, steroids, porphyries, etc.
The following compounds are applied as the organogermanium part of the complex: 1-hydroxy-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane, 1-thiohydroxy-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane, 1-methyl-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane-3,7-dione, 1-methyl-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane-3,7,10-trione, 1-hydroxy-1-germa-2,8,9-trithio-5-azatricyclo[3.3.3.01,5]undecane, 1-hydroxy-1-germa-2,8,9-trioxa-3-methyl-5-azatricyclo[3.3.3.01,5]undecane, 1-adamantyl-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane, 1-adamantyl-1-germa-2,8,9-trioxa-5-azatricyclo[3.3.3.01,5]undecane-3-one, 1-adamantyl-1-germa-2,8,9-trioxa-5-azatricyclo-[3.3.3.01,5]undecane-3,7-dione, etc.
All the known medicaments and biologically active compounds, which play an important role in vital activity of the human organism, form complexes with OGC, e. g.,
Antiviral medicaments: Midantanum, Remantadinum, Zidovodine (Retrovir), Virolex, Vidarabinum, Idoxuridine, Metisazonum, Oxolinum, Ganciclovir, Ribamidil;
Analgetic and antiinflammatory medicaments: acetylsalicylic acid, methylsalicylate, salicylamide, Mesalazine, Amidopyrinum, Analginum, Butadionum, Paracetamolum, Ibuprophenum, Naproxenum, Piroxicam, Sulindac, Dimexidum;
Antibacterial medicaments: Benzylpenicillinum-natrium, Oxacillinum-natrium, Ampicillinum, Cefaloridinum, Cefalexinum, Cefaclorum, Erythromycinum, Oleandomycini phosphas, Tetracyclinum, Oxytetracyclinum, Metacyclin, Laevomycetinum, Streptomycine sulfate, Neomycinum, Gentamycini sulfas, Sisomicini sulfas;
Sulfamide medicaments: Sulfadimezinum, Aethazolum, Urosulfanum, Sulphapyridazinum, Sulfadimethoxinum, Phtalazolum, etc.
Antituberculousis medicaments: Isoniacidum, Rifampicinum, Ethambutol, Ethionamide, Pirazinamide, Cycloserine, Florimicini sulfas;
Antitumor medicaments: Dopanum (Chlorethylaminouracil), Sarcolysinum (Racemelfalanum), Cyclophosphane, Chlorbutinum, Thiophosphamidum, Nitrosomethylurea, Myelosanum (Busulfan), Methotrexatum, Mercaptopurinum, Fluorouracil, Fluorofur, Dactinomycinum, Olivomycinum, Rubomycini hydrochloridum, Colchaminum, Vinblastine, Vincristine, Testosteroni propionas, Testoenatum, Synoestrolum, Phosphoestrolum, Aethyniloestradiolum, Hydrocortisonum, Prednisolone, Dexamethasonum, Triamcinolone, Cisplatin;
Antiepileptic medicaments: Phenobarbitalum, Dipheninum (Phenytoinum), Hexamidinum (Primidone), Sodium valproate, Lorazepam, Carbamazepin, Sibazonum (Diazepam), Trimethinum (Trimethadionum), Ethosuximidum;
Medicaments for Parkinson""s syndrome: Levodopa, Cyclodolum, Mydocalm, Bromocryptinum, Carbidopa, Benserazide;
Psychotropic medicaments: Aminazinum, Meterazinum, Aethaperazinum, Chlorprotexenum, etc.
Tranquilizers: Diazepam, Mezapamum, Phenazepamum (Fenazepam);
Nootropic medicaments: Aminalonum, Pyracetamum;
Vitamins: A, B1, B2, D2, D3, E, K1, K2, PP, B5, B6, B12, Bc, C, P;
Medicaments for treatment of schizophrenia: Aminazinum, Propazinum, Aethaperazinum;
Medicaments for treatment of cardiovascular system: Dibazolum, No-Spa, Papaverini hydrochloridum, Nitroglycerol, Erynitum, Validolum, Digitoxin, Celanidum, Quinidine Sulfate, Lidocaini hydrochloridum, Amiodaronum, Ornidum, Mesatonum, etc.
Aminoacids: glycine, alanine, valine, leucine, lysine, arginine, serine, cystine, etc.
Usage of the complexes for local applications as liniments and ointments is favorable to speeding-up of wounds healing, betterment of morphologic and biochemical properties of the granulation-fibrous tissue in injuries. Content of nucleic acids, collagen, glycoproteids including hexuronic acid has considerably increased in the tissue. Intensive cellular proliferation (DNA) combined with high biosynthetic activity (RNA).
Implementation of the same compounds considerably cuts duration for knitting of fractures and cracks of bones. It turns out that implementation of the complexes is beneficial for prophylaxis and medical treatment of caries, what is connected to the reparative effect of the complexes. Depending on a kind of the complex duration of knitting reduced 1.3÷1.7 times compared to the control case.
Complexes of OGC with aminoacids, vitamins, medicaments for treatment of cardiovascular system, nootropic medicaments, analgesic and antiinflammatory ones, medicaments from other groups have been examined.
Water solutions or suspensions of the complexes under investigation have been injected intraperitoneally 30÷60 min. before beginning of the experiment. Animals from the control group got equal amounts of physiological salt solution. High altitude hypoxia was made in special air tight chambers, in which a lift of the animals up to the altitude 10,000 m has been imitated by pumping out of air. A criterion of validity for the complexes was increase of mice life length and survivability of these. Individuals, which stayed alive at this altitude for more than 30 minutes and did not die after xe2x80x9cloweringxe2x80x9d, were considered as survived ones. Organogermanium complexes with analgesic and antiinflammatory medicaments: acetylsalicylic acid, Paracetamolum, Amidopyrinum, etc., antiviral medicaments: Remantadinum, Midantanum, etc., antibiotics: Benzylpenicillinum natrium, Ampicillinum, Cephalexine, etc., aminoacids: glycine, alanine, valine, leucine, lysine, arginine, etc., medicaments for treatment of cardiovascular system: Dibazolum, No- -Spa, Methyldopa (Sandoz, Switzerland), Celanidum, Verapamilum, etc., and also medicaments belonging to other groups have been investigated. These complex compounds in doses 5÷20 mg/kg increased life lengths for animals 2÷4 times compared to animals from the control group and were on the level of a standard antihypoxic medicamentxe2x80x94Mexaminum.
Interferon inducing activity of the complexes has been studied with various methods, including the study with native leukocytes of human donor blood. The complexes were stimulatory to interferon production, activity of which in tests made up 1000÷2000 IU. It is pertinent to note that for Interferon inducing compounds, which are known nowadays, this value makes up in average 500÷2000 IU.
Complexes of OGC with aminoacids, vitamins, medicaments for treatment of cardiovascular diseases, nootropic medicaments, analgetics and antiinflammatory medicaments, antibiotics and medicaments from other groups have been studied.
Antiinflammatory effect of complexes of medicaments and biologically active compounds with OGC has been studied by various methods including carrying out of clinical tests of ointments for contusions, strains and various inflammations.
Antiinflammatory effect has been studied for animals according to the method by Ju. Strel""nikov. Experiments have been carried out with white mice of mass 20 g. Aseptic inflammation was caused by injection of 0.1 ml of 2.5% formalin solution into thigh thickness of an animal""s paw. A compound under investigation was injected into the stomach in the dose equimolecular to 20 mg/kg of indometacin two hours before the injection of formalin. Distinction of the edema was estimated by increase of a mass of inflamed and uninflammed paws in experimental groups of animals compared to control ones. Control animals were mice which did not get the compounds under investigation. Simultaneously antiinflammatory activity of indometacin was studied for comparison. Realized pharmacological studies have shown that the complexes cause reduction of the edema depending on a kind of a medicament and OGC from 40 up to 70% compared to the control group. Indometacin reduced the edema by 33.4%.
Complexes of OGC with aminoacids, vitamins, medicaments for treatment of cardiovascular diseases, nootropic medicaments, analgetics and antiinflammatory medicaments, antibiotics and medicaments from other groups have been studied.
Nootropic properties have been studied using common procedures [1].
Decrease of toxic effects of the complexes of medicaments with OGC was studied for animals and also estimated when carrying out clinical investigations compared to the individual medicament. The following factors were under estimation:decrease of acute toxicity (LD50), decrease of side effect with non-allergic nature making up the spectrum of pharmacological effects for the medicament, decrease of side effect with allergic nature. Decrease of idiosyncrasy effects was also under estimation. Decrease of mutagenous, teratogenous and embryotoxic properties also was studied for the medicaments, which possess these side effects.
The complex toxicity of each individual medicament being considered as equal to 1, the toxicity of each complex medicament with OGC amounted to 0.15-0.6, depending on the kind of medicament and the kind of OGC.
Decrease of development of psychic and physical drug dependence also was estimated under implementation of a medicament with OGC compared to implementation of an individual medicament.
Taking into account expansion of therapeutic effect spectrum and increase of the main therapeutic effect, the total therapeutic index of a complex medicament increases by 3 to 5 times depending on the type of medicament and the kind of disease.